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The School of Medicine Named to Stand Up to Cancer Dream Team

Dreaming Big

Katie Couric (left) and Zhenge John Wang (right) at Stand Up to Cancer Dream Team grant announcement

Move over LeBron, Kyrie, and Kevin. There’s another dream team in town.

At an event hosted by Yahoo News global anchor Katie Couric earlier this month, Case Western Reserve University School of Medicine and Case Comprehensive Cancer Center were named to a new entertainment industry-led Stand Up to Cancer colorectal cancer dream team. The School of Medicine experts join scientists and clinicians from Memorial Sloan Kettering Cancer Center, Yale University, and Cornell University on the new team.

With the designation comes a $12 million award that will be shared among the four institutions. CWRU’s portion will support expanded testing of CB-839, a promising new colon cancer drug. The laboratory of Zhenghe John Wang, PhD, professor in the Department of Genetics and Genome Sciences at the School of Medicine, discovered CB-839’s potential effectiveness against a genetic subtype of colon cancer. (Wang is also co-leader of the GI Cancer Genetics Program at Case Comprehensive Cancer Center and a member of the SPORE team led by Sanford Markowitz, MD, PhD. The Case GI Specialized Program of Research Excellence is one of five nationally recognized GI SPORE centers in the country.)

Neal Meropol, MD, and Jennifer Eads, MD, members of the SPORE team, are currently testing CB-839 in patients at University Hospitals Seidman Cancer Center. The new grant will enable a substantial expansion of this clinical trial to Cleveland Clinic. In the trial, CB-839, a glutaminase inhibitor, is combined with capecitabine (a chemotherapy medication) in colorectal cancer patients whose tumors have mutations in the PIK3CA gene. The award will also support Wang’s expanded scientific studies of CB-839’s anti-cancer activity.

The dream team and grant were announced at the annual meeting of the American Association for Cancer Research in Washington DC.

“We are honored to be selected for the prestigious dream team and grant award,” said Wang. “On behalf of everyone at Case Western Reserve, we are grateful for the enormously important education and advocacy of Stand Up to Cancer and Ms. Couric, who has seen firsthand and supported the vital work being done on our campus. In everyday language, under this new grant we will try to starve colorectal cancer cells to death by depriving them of glutamine, a needed nutrient.”

Over a decade ago, Wang co-discovered that there are mutations of the PIK3CA gene (which is critical for cell division and movement) in 20 to 30 percent of colorectal cancers, suggesting that the mutations play a role in colorectal cancer. PIK3CA mutations are also found in other cancers, including breast cancer, raising the prospect of extending successful treatment of colorectal cancer to these other cancers.

Yujun Hao, PhD, a postdoctoral fellow in the Wang laboratory, recently discovered that PIK3CA mutations make colorectal cancer cells exceptionally dependent on glutamine, an amino acid that provides fuel (nitrogen and carbon) to the cancer cells. The Wang team found that blocking glutamine utilization in colorectal cancer cells that have PIK3CA mutations, in combination with the chemotherapy drug capecitabine, induced tumor regression in mice. They did not observe the same effect on tumors without the mutations. Now CWRU-linked clinicians are attempting to repeat those findings in human cancer patients.

“It’s a great honor to be part of this team,” said Eads, assistant professor of medicine. “This award gives us an unprecedented opportunity to join forces as we seek to have a major impact on this terrible disease. We are very grateful to all of the patients who are already taking part in the trial.”

Alok Khorana, MD, medical oncologist at Cleveland Clinic and professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, will also be participating in the clinical component. The trials are being carried out in concert with Case Comprehensive Cancer Center, led by its director, Stanton Gerson, MD, Asa and Patricia Shiverick-Jane Shiverick (Tripp) Professor of Hematological Oncology, and director of University Hospitals Seidman Cancer Center. “Dr. Wang, Dr. Eads, and the team are carrying out extremely important research and this award confirms the value of their efforts to date,” said Gerson. “Their work represents a rich opportunity for meaningful progress in our efforts against colorectal cancer and potentially, other forms of cancer as well.”

“After a national search, Wang's novel therapy was chosen as among the handful of the most promising new ideas in the country for better ways to treat colon cancer,” said Sanford Markowitz, MD, PhD, Markowitz-Ingalls Professor of Cancer Genetics at CWRU School of Medicine, medical oncologist at University Hospitals Cleveland Medical Center, principal investigator of the Case GI SPORE, and past member of the scientific advisory board of the National Colon Cancer Research Alliance founded by Couric. “This is a tremendous tribute to Drs. Wang and Eads and their colleagues, and to the SPORE mechanism that supported their efforts.”

Anthony Wynshaw-Boris, MD, PhD, professor and chairman of the Department of Genetics at CWRU School of Medicine, said: "The awarding of the colorectal cancer dream team grant to John Wang and his colleagues is a remarkable accomplishment. They truly are a dream team of gifted cancer translational researchers. The investigation of tailored treatments for novel subgroups of colorectal cancer, based on genetic differences, is a fantastic example of precision medicine."

Other CWRU School of Medicine investigators on the dream team include Markowitz and Joseph Willis, MD, professor and vice chair of the Department of Pathology and chief of pathology at University Hospitals Cleveland Medical Center; Jill Barnholtz-Sloan, PhD, Sally S. Morley Designated Professor in Brain Tumor Research and associate director for bioinformatics at Case Comprehensive Cancer Center; and Kishore Guda, DVM, PhD, assistant professor in the Division of General Medical Sciences-Oncology at Case Comprehensive Cancer Center.

The new dream team joins Stand Up to Cancer’s 19 other dream teams, three of which are working to improve detection, diagnosis, and treatment of colorectal cancer. The National Cancer Institute estimates that 4.5 percent of all men and women in the United States will be diagnosed with colorectal cancer during their lifetimes, making it the third most common non-skin cancer.

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